1. Field of the Invention
The present invention is directed to oligonucleotides which include modified bases-such that members of a matched pair of the oligonucleotides are unable to form stable hybrids with one another and yet are able to form stable, sequence specific hybrids with complementary unmodified DNA or RNA strands. The present invention is also directed to the use of such oligonucleotides as an anti-sense and anti-gene agents and probes for specific sequences in single or double stranded DNA or RNA.
2. Brief Description of Prior Art
It is well known that oligonucleotides (ODNs) do not readily hybridize to complementary sequences in double stranded DNA or in DNA or RNA secondary structure. Nevertheless, it is also known that the ability to sequence specifically access double stranded DNA or single stranded RNA or DNA in secondary structure would have great utility in gene mapping, diagnostics and therapeutic applications. Methods known in the prior art which, although limited in scope, accomplish hybridization of ODNs to duplex nucleic acids include triplex formation (see Troel. S. et al. Science 1991, 254, 1639), the branch capture reaction (Weinstock, P. et al. Nucl. Acids Res. 1990, 18, 4207), recombinase mediated synapsis (Roca, A. I.; et al. Rev. Biochem. Mol. Biol. 1990, 25, 415) and cross-linking of the hybridized ODN to at least one strand of the duplex nucleic acid (PCT application WO 93/03736, published Mar. 4, 1993).
There is however still a significant need, and room for improvement in the art, for oligonucleotides which are able to sequence specifically hybridize to duplex nucleic acids. The present invention provides such oligonucleotides.